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So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with\n                      <jats:sc>l<\/jats:sc>\n                      \u2010citrulline in Dahl salt\u2010sensitive rats, a model of superimposed preeclampsia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Parental Dahl salt\u2010sensitive rats were treated with\n                      <jats:sc>l<\/jats:sc>\n                      \u2010citrulline (2.5\u00a0g\u00b7L\n                      <jats:sup>\u22121<\/jats:sup>\n                      in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt\u2010sensitive rats was assessed by wire myograph.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In Dahl salt\u2010sensitive rats,\n                      <jats:sc>l<\/jats:sc>\n                      \u2010citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms\u2010like tyrosine kinase 1.\n                      <jats:sc>l<\/jats:sc>\n                      \u2010Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium\u2010derived hyperpolarizing factor\u2010mediated vasorelaxation in resistance arteries.\n                      <jats:sc>l<\/jats:sc>\n                      \u2010Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition,\n                      <jats:sc>l<\/jats:sc>\n                      \u2010citrulline down\u2010regulated genes involved in the TLR4 and NF\u2010\u03baB signalling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      This study shows that\n                      <jats:sc>l<\/jats:sc>\n                      \u2010citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia.\n                      <jats:sc>l<\/jats:sc>\n                      \u2010Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15783","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T03:42:55Z","timestamp":1640144575000},"page":"3007-3023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>l<\/scp>\n                    \u2010Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-6479","authenticated-orcid":false,"given":"Andy W. 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